FIGURE 5.

CircHIPK3 knockdown or its combined application with ATO alleviated the symptoms and joint destruction of CIA mice. (A) Representative pictures of the paws of mice showed that CIA developed rapidly in paws after the mice were immunized with collagen II and sustained to the end of the experiment. AAV-sh-circHIPK3, 2.0 mg/kg/day ATO administration, or the combination treatment of above two agents significantly alleviated the severity of arthritis compared with the CIA group on day 33 (Ⅰ) and day 39 (Ⅱ) after the first immunization. (B) The micro-CT images of paws demonstrated the destruction of the bone and cartilage in CIA mice, and ATO injection alleviated the joint destruction. AAV-sh-circHIPK3 intra-articular therapy in addition to ATO could evidently reduce the damages of bone compared with ATO therapy alone. (C) Clinical evaluation and the process diagram are demonstrated. Clinical arthritis scores showed that both ATO and intra-articular AAV-sh-circHIPK3 therapy could significantly reduce the arthritis scores of CIA mice. Moreover, combining ATO and AAV-sh-circHIPK3 reduced the arthritis score more significantly than ATO treatment alone (n = 5; *p < 0.05, **p < 0.01, ***p < 0.001 versus PBS group). Data are expressed as the mean ± SEM.